Molecular switch-like regulation enables global subunit coordination in a viral ring ATPase

Sara Tafoya, Shixin Liu, Juan P. Castillo, Rockney Atz, Marc C. Morais, Shelley Grimes, Paul J. Jardine, Carlos Bustamante

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Subunits in multimeric ring-shaped motors must coordinate their activities to ensure correct and efficient performance of their mechanical tasks. Here, we study WT and arginine finger mutants of the pentameric bacteriophage φ29 DNA packaging motor. Our results reveal the molecular interactions necessary for the coordination of ADP–ATP exchange and ATP hydrolysis of the motor’s biphasic mechanochemical cycle. We show that two distinct regulatory mechanisms determine this coordination. In the first mechanism, the DNA up-regulates a single subunit’s catalytic activity, transforming it into a global regulator that initiates the nucleotide exchange phase and the hydrolysis phase. In the second, an arginine finger in each subunit promotes ADP–ATP exchange and ATP hydrolysis of its neighbor. Accordingly, we suggest that the subunits perform the roles described for GDP exchange factors and GTPase-activating proteins observed in small GTPases. We propose that these mechanisms are fundamental to intersubunit coordination and are likely present in other ring ATPases.

Original languageEnglish (US)
Pages (from-to)7961-7966
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number31
DOIs
StatePublished - Jul 31 2018

Bibliographical note

Funding Information:
and application of step-finding algorithms). This work is also funded, in part, by National Institute of Health grants R01GM071552 (fluorescent protein FRET characterization) and R01GM032543 (fluorescent protein X-ray characterization), and by the Howard Hughes Medical Institute (fluorescent protein counting). S.T. acknowledges the University of California Institute for Mexico and the United States (UC MEXUS) for a graduate fellowship, S.L. acknowledges support from US NIH Pathway to Independence Award R00-GM107365, and J.P.C. acknowledges the Pew Scholar Fellowship.

Funding Information:
ACKNOWLEDGMENTS. We thank Lisa Alexander, Varsha Desai, Ronen Gabizon, Liang Meng Wee, and Shannon Yan for helpful discussion of the paper. C.B. acknowledges support from the Nanomachines program (KC1203) funded by the Director, Office of Science, Office of Basic Energy Sciences of the US Department of Energy (DOE) contract no. DE-AC02-05CH11231 (development

Funding Information:
We thank Lisa Alexander, Varsha Desai, Ronen Gabizon, Liang Meng Wee, and Shannon Yan for helpful discussion of the paper. C.B. acknowledges support from the Nanomachines program (KC1203) funded by the Director, Office of Science, Office of Basic Energy Sciences of the US Department of Energy (DOE) contract no. DE-AC02-05CH11231 (development and application of step-finding algorithms). This work is also funded, in part, by National Institute of Health grants R01GM071552 (fluorescent protein FRET characterization) and R01GM032543 (fluorescent protein X-ray characterization), and by the Howard Hughes Medical Institute (fluorescent protein counting). S.T. acknowledges the University of California Institute for Mexico and the United States (UC MEXUS) for a graduate fellowship, S.L. acknowledges support from US NIH Pathway to Independence Award R00-GM107365, and J.P.C. acknowledges the Pew Scholar Fellowship.

Keywords

  • Intersubunit enzymatic regulation
  • Molecular switch-like regulation
  • Ring ATPases
  • Ring-shaped molecular motors
  • Single molecule DNA packaging

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